title: Multimodal imaging of nanovaccine carriers targeted to human dendritic cells.
abstract: Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy against cancer and infectious diseases. The targeted delivery of nanovaccine particles (NPs) to DCs in vivo is a promising strategy to enhance immune responses. Here, targeted nanovaccine carriers were generated that allow multimodal imaging of nanocarrier-DC interactions from the subcellular to the organism level. These carriers were made of biodegradable poly(D,L-lactide-co-glycolide) harboring superparamagnetic iron oxide particles (SPIO) and fluorescently labeled antigen in a single particle. Targeted delivery was facilitated by coating the NPs with antibodies recognizing the DC-specific receptor DC-SIGN. The fluorescent label allowed for rapid analysis and quantification of specific versus nonspecific uptake of targeted NPs by DCs compared to other blood cells. In addition, it showed that part of the encapsulated antigen reached the lysosomal compartment of DCs within 24 h. Moreover, the presence of fluorescent label did not prevent the antigen from being presented to antigen-specific T cells. The incorporated SPIO was applied to track the NPs at subcellular cell organel level using transmission electron microscopy (TEM). NPs were found within endolysosomal compartments, where part of the SPIO was already released within 24 h. Furthermore, part of the NPs seemed to localize within the cytoplasm. Ex vivo loading of DCs with NPs resulted in efficient labeling and detection by MRI and did not abolish cell migration within collagen scaffolds. In conclusion, incorporation of two imaging agents within a single carrier allows tracking of targeted nanovaccines on a subcellular, cellular and possibly organism level, thereby facilitating rational design of in vivo targeted vaccination strategies.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Cruz
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tacken
authors.forename: Fernando
authors.initials: F
authors.lastname: Bonetto
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Buschow
authors.forename: Huib J
authors.initials: HJ
authors.lastname: Croes
authors.forename: Mietske
authors.initials: M
authors.lastname: Wijers
authors.forename: I Jolanda
authors.initials: IJ
authors.lastname: de Vries
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
mesh_terms: D017951:Antigen Presentation; D001773:Blood Cells / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004337:Drug Carriers; D005290:Ferric Compounds / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D036103:Nanotechnology; D010446:Peptide Fragments / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D004337:Drug Carriers; D005290:Ferric Compounds; D019344:Lactic Acid; D037181:Lectins, C-Type; D058185:Magnetite Nanoparticles; D010446:Peptide Fragments; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011956:Receptors, Cell Surface; D022223:Vaccines, Subunit; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C000499:ferric oxide